Hepatitis C Virus (HCV) is now recognized as being the primary cause of transfusion associated non A, non B (NANB) hepatitis. HCV is a single stranded, positive sense RNA virus with similarities to flaviviruses and pestiviruses (Miller R H and Purcell R H. Proc Natl Acad. Sci. (1991) 87, 2057; Weiner A J, et al. Virology (1990) 180, 842) and is in global distribution. HCV contains a plus-strand RNA genome of approximately 10,000 nucleotides that encodes a polyprotein precursor of about 3000 amino acids. The polyprotein is co- and post-translationally processed by cellular and viral proteases into mature structural and non-structural proteins. The structural proteins include the core protein and the envelope glyco-proteins, E1 and E2. The non-structural proteins include the NS2-3 auto-protease, the NS3 serine protease, a NTPase/RNA helicase domain in the carboxy terminal two-thirds of NS3, the NS4A polypeptide, the NS4B and NS5A proteins, and the NS5B RNA-dependent RNA polymerase. The HCV genome is heterogeneous and has been classified into six major genotypes (1-6), whose nucleotide and deduced amino acid sequences vary by about 30% over the entire genome (see, Neville, J. A. et al., J. Clin. Microbiol., 35:3062-3070 (1997)).
Infection with HCV is currently diagnosed by direct detection of viral RNA by PCR or by detection of anti-HCV antibodies (generally to the HCV structural core protein or non-structural NS3 protein). More recently HCV antigen assays have been developed which demonstrate that HCV core protein antigens can be detected in a sample sooner than antibodies can be detected. Studies have shown that the average time from the first viremic bleed to the first HCV antigen positive bleed is estimated at 2.0 days and that the average time to the first HCV antibody positive bleed at 50.8 days (Couroucé A M, et al. Transfusion, (2000) 40, 1198-1202).
Currently available HCV test kits that employ anti-HCV antibodies use monoclonal antibodies. Monoclonal antibodies (mAbs) have been emerging over recent years as increasingly important commercial reagents (see, Smith, K. A., et al., J. Clin. Pathol., 57:912-917 (2004)), especially in the area of diagnostics and therapeutics where the exceptionally high degree of directional binding exhibited by mAbs has contributed to their success.
Recent developments in recombinant DNA technology have made it possible to clone the sequences encoding mAbs and to express the antibodies, or fragments of the antibodies, as recombinant proteins. Recombinant antibodies can often be produced more consistently and reliably from recombinant constructs than from the original hybridoma. Recombinant DNA technology has also allowed the creation of combinations of the heavy and light chain variable regions of a desired non-human mAb with human constant regions creating a chimeric antibody (see, for example, U.S. Pat. Nos. 4,816,567 and 6,331,415). The chimeric antibody retains the specificity and affinity of the original non-human monoclonal antibody but causes lower human anti-murine antibody (HAMA) responses when administered therapeutically and also is capable of reacting in existing diagnostic assay formats that measure human immunoglobulin.
Monoclonal and recombinant antibodies to HCV have been described. For example, U.S. Pat. Nos. 5,595,868 and 7,049,060, and U.S. Patent Application 2003/0148333 describe monoclonal antibodies to HCV core protein; U.S. Patent Application 2004/0208887 describes monoclonal antibodies to HCV E1 protein; U.S. Pat. Nos. 5,308,750 and 7,091,324 describe monoclonal antibodies to HCV E2 protein; and U.S. Pat. No. 5,753,430 describes monoclonal antibodies to HCV core protein, NS3 protein and NS4 protein. Human recombinant antibodies, and specifically Fab fragments derived from human antibodies, specific for HCV NS3 protein are described in U.S. Patent Application 2004/0214994. Chimeric antibodies to the hypervariable region 1 (HVR1) of HCV have been described (Li, C. and Allain, J-P., J. Gen. Virol., 86:1709-1716 (2005)). HVR1 is a highly mutated region of 27 residues at the N-terminus of the E2 protein.
The use of “heterologous” chimeric antibodies as quality control reagents or calibrators of immunoassays has been described (Hamilton, R. G., Ann. Biol. Clin., 48:473-477 (1990); Hamilton, R. G., Ann. Biol. Clin., 49:242-248 (1991); Naess, L. M., et al., J. of Immunol. Methods, 196:41-49; Schuurman, J., et al., J. Allergy Clin. Immunol., 99:545-550 (1997)). Heterologous in this context indicates that the chimeric antibody binds to an antigen unrelated to the antigen used in the assay for antibody detection. The use of recombinant mouse-human chimeric antibodies, and specifically recombinant mouse-human chimeric antibodies against Toxoplasma gondii, that bind to same or “homologous” antigen as calibrators or positive controls in assays and kits that measure human antibodies has also been described (U.S. Pat. No. 6,015,662 and Hackett, J. Jr., et al., J. Clin. Microbiol., 36:1277-1284)).
Moreover, many HCV immunoassays use HCV infected patient blood samples to prepare a HCV sensitivity panel. Quality control reagents such as sensitivity panels are human plasma/serum screened for the presence of antibodies against specific epitopes. However, the use of human serum/plasma has several significant disadvantages, including increased regulatory concerns, difficulty in sourcing large volume with high-titer and specificity, lot-to-lot variability, limitations with respect to characterization, and cost.
This background information is provided for the purpose of making known information believed by the applicant to be of possible relevance to the present invention. No admission is necessarily intended, nor should be construed, that any of the preceding information constitutes prior art against the present invention.